Protective Role of rAAV-NDI1, Serotype 5, in an Acute MPTP Mouse Parkinson's Model.
Protective Role of rAAV-NDI1, Serotype 5, in an Acute MPTP Mouse Parkinson's Model.
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DOI：
10.4061/2011/438370
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发表时间：
2010-12-06
期刊：
影响因子：
--
通讯作者：
Yagi T
中科院分区：
文献类型：
--
作者：
Barber-Singh J;Seo BB;Matsuno-Yagi A;Yagi T
线粒体质子转运型NADH-Q氧化还原酶(复合体I)的缺陷与许多获得性和遗传性疾病有关，包括Leigh综合征和最近的帕金森病。已经尝试了有限数量的策略来修复受损的复合体I，但收效甚微或毫无成功。我们最近成功地将酿酒酵母(Saccharmyces Cerevisiae)内含的非质子泵的NADH-泛醌氧化还原酶(Ndi1)插入到小鼠和大鼠的线粒体中，并发现该酶具有完全的活性。利用携带NDI1基因的重组腺相关病毒载体(血清型5)，我们在C57BL/6小鼠的黑质(SN)中表达了NDI1蛋白，表达周期为2个月。结果表明，与使用血清2型的以前的模型相比，AAV血清5型在SN中高效地表达Ndi1，这导致在使用急性MPTP模型时几乎100%的保护。可以想象，携带NDI1基因的AAV血清型5是一种强有力的概念验证研究工具，可以证明复杂的I缺陷是脑部疾病的致病因素。
Defects in mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) have been implicated in a number of acquired and hereditary diseases including Leigh's syndrome and more recently Parkinson's disease. A limited number of strategies have been attempted to repair the damaged complex I with little or no success. We have recently shown that the non-proton-pumping, internal NADH-ubiquinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae (baker's yeast) can be successfully inserted into the mitochondria of mice and rats, and the enzyme was found to be fully active. Using recombinant adenoassociated virus vectors (serotype 5) carrying our NDI1 gene, we were able to express the Ndi1 protein in the substantia nigra (SN) of C57BL/6 mice with an expression period of two months. The results show that the AAV serotype 5 was highly efficient in expressing Ndi1 in the SN, when compared to a previous model using serotype 2, which led to nearly 100% protection when using an acute MPTP model. It is conceivable that the AAV-serotype5 carrying the NDI1 gene is a powerful tool for proof-of-concept study to demonstrate complex I defects as the causable factor in diseases of the brain.
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影响因子：
3.7
作者：
Marella M;Seo BB;Thomas BB;Matsuno-Yagi A;Yagi T
通讯作者：
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影响因子：
168.9
作者：
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作者：
Marella, Mathieu;Seo, Byoung Boo;Yagi, Takao
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影响因子：
4.2
作者：
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Petzinger, GM
影响因子：
3.3
作者：
Abrous, DN;Rodriguez, JJ;Barneoud, P
通讯作者：
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